The surface antigens of Paramecium tetraurelia are specified by a family of 11 genes. The main purpose of this project is to discover the molecular mechanisms involved in the genetic, cytoplasmic and environmental control of these genes. We believe that such information will help contribute to one of the major problems of biology and basic medicine today--how gene expression is controlled in eukaryotes. The study involves cloning the genes and their mutants in order to compare their structure in the expressed and non-expressed states. Neighboring chromosomal regions will be included in the study. Genes which differ in stability of expression will be characterized genetically and molecularly in a search for clues to the sites primarily responsible for whether the genes are turned off or on. Cytoplasmic transfers will be made by microinjection in order to find cytoplasmic regulator molecules whose existence has been inferred from genetic work. Attempts will also be made to identify the regulator molecules by their postulated capacity to bind to the cloned genes. Finally, an attempt will be made to associate directly the cloned genes with their products.